We are studying various aspects of the birth, life and death of T cells. BIRTH-1) For years scientists have looked for a self-renewing stem cell in the thymus and failed to find one. We found that intact fetal thymuses, placed under the kidney capsules of SCID mice, continued to produce T cells for at least 6 months. We are now studying whether the loss of this stem cell activity seen in the older experiments is due to age of the cells, the age and/or irradiated state of the recipient thymus, or the in vitro purification treatments. 2) In the presence of IL-7, the differentiation of alphaBeta, but not gamma delta T cells is reversibly blocked in thymic organ cultures. We hypothesize that the levels of this lymphokine may regulate the rate at which alphaBeta T cells are produced. LIFE:1) Using mice primed before or after thymectomy, we found that virgin mice can only be primed for about 5 months after thymectomy, but mice primed before thymectomy respond for at least 4 months, at which time they still contain large number of cells expressing a 'virgin' surface phenotype, among which are a large number of functionally immunized CTL. 2) CTL to some Ags (usually viruses) do not seem to need help from CD4 T cells while CTL to other ags, (usually cellular Ags), are strictly help dependent. We have postulated that CTL activation by dendritic cells or activated APCs may bypass CD4 help & that some viruses may directly activate APCs. To test this hypothesis, we have immunized animals with purified dendritic cells under conditions where CD4 T cell help is limiting. We found that this procedure works in some cases & not in others & are now characterizing the differences. DEATH-1) We found that thymic epithelium (TE) induces tissue specific tolerance in developing thymocytes & that this tolerance does not extend to skin specific antigens. Yet an animal is tolerance of its own skin. We are ow determining whether this particular skin antigen is found on bone marrow cells. If not, then one must begin to ask how an individual is tolerant of its own skin. 2) By grafting 2 sets of congenic fetal thymuses into normal & SCID recipients, we found that the mature thymic T cell population may contain up to 10% recirculating T cells, that the recirculating population contains both activated & resting cells, with a rather high proportion of gamma delta cells. We are now testing whether the recirculating population ever exists the thymus again and whether, during its thymic sojourn, it is activated or tolerized by antigens not expressed in the thymus in which it matured.